A novel preparation of 2-aminocyclopentanecarboxamides

Article abstract of DOI:10.1007/s007060200077

Different syntheses of cis- and trans-2-aminocyclopentanecarboxamides were studied. A convenient and effective method was devised for the preparation of cis-2-aminocyclopentanecarboxamide derivatives starting from the readily available 6-tert-butoxycarbon

Full text of DOI:10.1007/s007060200077

Monatshefte fuÈr Chemie 133, 1077±1084 ꢀ2002)
A Novel Preparation
of 2-Aminocyclopentanecarboxamides
1
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Peter Csomos , Gabor Bernath and Ferenc Fulop
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1
Institute of Pharmaceutical Chemistry, University of Szeged, H-6720 Szeged, Hungary
Research Group for Heterocyclic Chemistry of the Hungarian Academy of Sciences
and the Universityof Szeged, H-6720 Szeged, Hungary
2
Summary. Different syntheses of cis- and trans-2-aminocyclopentanecarboxamides were studied.
A convenient and effective method was devised for the preparation of cis-2-aminocyclopentane-
carboxamide derivatives starting from the readilyavailable 6- tert-butoxycarbonyl-6-azabicy-
clo[3.2.0]heptan-7-one.
Keywords. ꢀ-Amino acids; cis-trans Isomerization; ꢀ-Lactams; Small rings.
Introduction
In recent years, a number of cyclic ꢀ-aminocarboxylic acid derivatives have been
synthesized. Some of them have useful pharmacological effects, and they are
widely used synthons for the preparation of saturated 1,3-heterocycles [1]. Various
cis- and trans-2-aminocycloalkanecarboxamides have been produced in order to
examine the relations between stereochemistryand pharmacological activity[2, 3]
by the mixed anhydride method from N-protected 2-aminocycloalkanecarboxylic
acids [3±8] or by amidation of alkyl 2-aminocycloalkanecarboxylates [9, 10].
The discoveryof the antimycotic cispentacin, ꢀ-)-ꢀ1 R,2S)-2-aminocyclopen-
tanecarboxylic acid, among the natural amino acids aroused interest in inves-
tigations of cyclopentane derivatives [11], and the synthesis, transformations, and
some of the biological features of 2-aminocyclopentanecarboxylic acids have
been reviewed [12, 13]. During our investigations relating to cispentacin [13, 14],
our aim was to prepare carboxamide derivatives of racemic cis- and trans-2-
aminocyclopentanecarboxylic acids and to study the ring opening of the starting
6-azabicyclo[3.2.0]heptan-7-one and its N-tert-butoxycarbonyl derivative.
Results and Discussion
A simple and mild amidation procedure has been developed earlier in our
laboratoryfor the preparation of 2-aminocyclohexanecarboxamides starting from
the corresponding ethyl 2-aminocyclohexanecarboxylates [10]. Surprisingly, with
Ã
Corresponding author. E-mail: fulop@pharma.szote.u-szeged.hu

ꢀ
P. Csomos et al.
1078
Scheme 1
the same method ꢀ25% methanolic ammonia at room temperature) the homo-
logue ethyl cis-2-aminocyclopentanecarboxylate 1 resulted in a mixture of cis-
2-aminocyclopentanecarboxamide ꢀ2a) and the corresponding trans isomer 3a
ꢀScheme 1). The 1H NMR spectrum of the crude product revealed a 4:1 mixture of
2a and 3a.
This fact led us to reinvestigate our earlier results; however, in accordance with
those ®ndings [10], no isomerization was observed in the amidation of ethyl cis-
and trans-2-aminocyclohexanecarboxylates.
The isomerization of 2a was also investigated. In the presence of 0.5
equivalents of sodium methoxide at 150ꢀC, a mixture of 2a and 3a was obtained in
a ratio of 1:9. From this mixture, the hydrochloride was prepared; it was recrys-
tallized from ethanol=diethyl ether, furnishing 3b ꢀScheme 2).
When 6-azabicyclo[3.2.0]heptan-7-one ꢀ4), readilyavailable bycycloaddition
of chlorosulfonyl isocyanate to cyclopentene [13, 16], was re¯uxed in dry ethanol
with sodium ethoxide and the intermediate esters were hydrolyzed, cis- and trans-
2-aminocyclopentanecarboxylic acids 5 and 6 were obtained in a ratio of 1:9. This
mixture was recrystallized from ethanol and water, affording 6 in moderate overall
yield. Esteri®cation of trans-2-aminocyclopentanecarboxylic acid provided the
hydrochloride of ethyl trans-2-aminocyclopentanecarboxylate ꢀ7). The amidation
of 7 in 25% methanolic ammonia at room temperature gave trans-2-aminocyclo-
pentanecarboxamide 3a as a single product ꢀScheme 2).
Scheme 2. i) 1.2 equiv. NaOEt, EtOH, re¯ux, 12 h; ii) 18% HCl, re¯ux, 24 h; iii) ion-exchange
chromatography, recrystallization; iv) SOCl2, EtOH, <À10ꢀC, r.t., 3 h, re¯ux, 1 h; v) 25%
NH3=MeOH, 3 weeks; vi) 150ꢀC, 0.5 equiv. NaOEt, 10 min, puri®cation as HCl salt by
recrystallization

2-Aminocyclopentanecarboxamides
1079
Scheme 3. i) conc. HCl, r.t., 1 h; ii) Z±Cl, NaOH=H2O; iii) ethyl chloroformate, Et3N, toluene,
<À10ꢀC; iv) 25% NH3=MeOH, <À10ꢀC; v) HBr=AcOH, r.t., 1 h; vi) 10% Pd=C, H2, MeOH, 1 atm,
40ꢀC; vii) Boc2O, DMAP, CH2Cl2, r.t., 17 h; viii) 25% NH3=MeOH, 4ꢀC, 12 h; ix) benzylamine, dry
toluene, 24 h re¯ux; x) 3 M HCl=EtOH, r.t., 2 h; xi) 25% NH3=MeOH, r.t., 3 weeks
For the preparation of amide 2a, a 0.1 mol scale method was devised involving
the mixed anhydride procedure ꢀScheme 3). Compound 2a has also been prepared
bythis method earlier [6], but no experimental details and physical data were
given. The Z-protected amino acid 8 reacted with ethyl chloroformate to give the
anhydride which was allowed to react with 2 equivalents of ammonia in methanol.
The protective Z-group was eliminated with 33% hydrobromic acid in glacial
acetic acid or by hydrogenolysis with 10% palladium on activated charcoal.
No reaction was observed between ꢀ-lactam 4 and methanolic ammonia at
room temperature. Although activated monocyclic derivatives can be opened with
different amines [15], it was argued that byactivating the lactam ring with the
protecting group Boc the amidation reaction might be achieved under mild
conditions. The reaction of the N-Boc derivative of the bicyclic ꢀ-lactam 10 with
25% methanolic ammonia was complete after 12 h at 4ꢀC, resulting in the cis-
carboxamide 11. In this reaction no isomerization was observed. The Boc group
was easilyremoved by3 M hydrogen chloride in dry ethanol at room temperature,
affording the hydrochloride 2b.
When 10 was reacted with benzylamine at elevated temperature, benzamide 12
was formed in good yield. After removal of the Boc group, the benzamide 13 was
obtained.
Experimental
Melting points were determined on a Ko¯er melting point apparatus and are uncorrected. 6-
Azabicyclo[3.2.0]heptan-7-one ꢀ4) was prepared by 1,2-dipolar cycloaddition of chlorosulfonyl
isocyanate to cyclopentene; from this, cis-2-aminocyclopentanecarboxylic acid hydrochloride was
obtained by acidic hydrolysis [16].

ꢀ
P. Csomos et al.
1080
1
The H and 13C NMR spectra were recorded in CDCl3 or D2O solution in 5 mm tubes at room
temperature on a Bruker Avance DRX-400 spectrometer at 400.13 ꢀ1H) and 100.61 ꢀ13C) MHz,
utilizing the deuterium signal of the solvent for the ®eld-frequencylock and TMS as internal
standard. Elemental analyses were found to agree satisfactorily with the calculated data.
trans-2-Aminocyclopentanecarboxylic acid ꢀ6; C6H12NO2)
To a solution of 3.3 g 4 ꢀ30 mmol) in 50 cm3 dryEtOH, 2.5 g EtONa ꢀ36 mmol) were added, and the
mixture was re¯uxed for 12 h. The solvent was evaporated, and the residue was dissolved in 50 cm3
18% HCl and re¯uxed for 24 h. After evaporation to dryness, the residue was dissolved in 30 cm3
MeOH, and the inorganic salt was ®ltered off. The MeOH was evaporated, and the residue was
puri®ed on Varion KS ion-exchange resin. The 1H NMR spectrum of the crude product revealed the
presence of cis- and trans-2-aminocyclopentanecarboxylic acids 5 and 6 in a 1:9-ratio. This mixture
was recrystallized, affording 3.04 g trans-2-aminocyclopentanecarboxylic acid 6 ꢀ78%).
1
Colourless crystals; m.p.: 262ꢀC ꢀ90% EtOH; Ref. [17]: m.p.: 239±240ꢀC); H NMR ꢀD2O):
ꢁ ˆ 1.65±2.20 ꢀm, 3  CH2), 2.68 ꢀm, H-1), 3.77 ꢀm, H-2) ppm; 13C NMR ꢀD2O): ꢁ ˆ 23.0 ꢀC4), 29.7
ꢀC5), 30.6 ꢀC3), 51.9 ꢀC1), 55.3 ꢀC2), 181.7 ꢀCOOH) ppm.
Ethyl trans-2-aminocyclopentanecarboxylate hydrochloride ꢀ7; C8H16ClNO2)
Thionyl chloride ꢀ0.56 cm3, 7.6 mmol) was added dropwise under stirring to 7 cm3 dryEtOH below
À10ꢀC, followed by0.9 g ꢀ7 mmol) 6 in one portion, and the mixture was stirred for 30 min at 0ꢀC.
After stirring for additional 3 h at room temperature, the mixture was re¯uxed for 1 h and evaporated.
To the brown oilyresidue, diethyl ether was added, and upon standing at À18ꢀC 1.06 g of a white
crystalline powder was obtained ꢀ78%).
M.p.: 67±72ꢀC ꢀEtOAc); 1H NMR ꢀD2O): ꢁ ˆ 1.26 ꢀt, J ˆ 7.2, CH2CH3), 1.62±2.32 ꢀm,
3  CH2), 2.96 ꢀm, H-1), 3.90 ꢀm, H-2), 4.20 ꢀq, J ˆ 7.2, CH2CH3) ppm; 13C NMR ꢀD2O): ꢁ ˆ 13.7
ꢀCH3), 23.1 ꢀC4), 29.0 ꢀC5), 30.9 ꢀC3), 48.8 ꢀC1), 54.3 ꢀC2), 62.8 ꢀCH2CH3), 175.7 ꢀCOO) ppm.
trans-2-Aminocyclopentanecarboxamide ꢀ3a; C6H12N2O)
Ethyl trans-2-aminocyclopentanecarboxylate ꢀ7; 0.46 g, 2.93 mmol) was dissolved in 10 cm3 of 25%
ammonia in dryMeOH. The solution was kept at room temperature for 3 weeks. The solvent was
then evaporated, and the white crystalline powder was recrystallized resulting in 0.28 g 3a ꢀ74%).
1
Colourless crystals; m.p.: 123±124ꢀC ꢀEtOAc); H NMR ꢀCDCl3): ꢁ ˆ 1.32±2.22 ꢀ3  CH2),
1.59 ꢀbs, CHNH2), 2.25 ꢀm, H-1), 3.24 ꢀm, H-2), 5.50 ꢀbs, CONH2), 7.05 ꢀbs, CONH2) ppm; 13C
NMR ꢀCDCl3): ꢁ ˆ 22.4 ꢀC4), 27.2 ꢀC5), 37.9 ꢀC3), 53.3 ꢀC1), 58.0 ꢀC2), 178.0 ꢀCONH2) ppm.
cis-2-Benzyloxycarbonylaminocyclopentanecarboxylic acid ꢀ8; C14H17NO4)
cis-2-Aminocyclopentanecarboxylic acid hydrochloride ꢀ49.7 g, 0.3 mol) was dissolved under
stirring in 120 cm3 10% NaOH, and a few crystals of phenolphthalein were added. The solution was
cooled with ice-H2O, and 61.4 g benzyl chloroformate ꢀ0.36 mol) and 10% NaOH were then added in
parallel dropwise during 1 h; care was taken that the reaction mixture always remained slightly
alkaline. Stirring was continued at 0ꢀC for 1 h and for further 4 h at room temperature. The excess
benzyl chloroformate was next removed from the mixture by extraction with 100 cm3 diethyl ether.
The aqueous phase was cooled in ice and acidi®ed to pH 2 with 18% HCl. The oil that separated was
extracted with 3 Â 200 cm3 CHCl3. The organic phase was dried ꢀNa2SO4), ®ltered, and evaporated.
Trituration of the oilyresidue with n-hexane gave 55.3 g 8 as a white crystalline powder ꢀ70%). After
®ltration, the powder was used for the next step. A small sample was puri®ed byrecrystallization
from diisopropyl ether.

2-Aminocyclopentanecarboxamides
1081
Colourless crystals; m.p.: 92±94ꢀC; 1H NMR ꢀCDCl3): ꢁ ˆ 1.48±2.12 ꢀ3  CH2), 3.03 ꢀm, H-1),
4.26 ꢀm, H-2), 5.11 ꢀm, NCH2Ph), 7.20±7.48 ꢀm, 5  CH) ppm; 13C NMR ꢀCDCl3): ꢁ ˆ 22.6, 23.3
ꢀC4), 28.1, 28.5 ꢀC5), 32.2, 32.6 ꢀC3), 47.1 ꢀC1), 54.9, 55.9 ꢀC2), 67.5, 68.3 ꢀOCH2Ph), 128.8, 129.2
ꢀPh, C20±C60), 137.1 ꢀPh, C10), 156.7, 158.8 ꢀNHCOO), 179.0, 179.9 ꢀCOOH) ppm.
cis-2-Benzyloxycarbonylaminocyclopentanecarboxamide ꢀ9; C14H18N2O3)
To a salt-ice cooled, intensivelystirred solution of 31.6 g 8 ꢀ0.12 mol) and 12.1 g triethylamine
ꢀ0.12 mol) in 400 cm3 drytoluene, 13.0 g ethyl chloroformate ꢀ0.12 mol) was added dropwise below
À10ꢀC. After 15 min at À10ꢀC, 16.3 g 25% ammonia in dryMeOH ꢀ0.24 mol NH 3) was added in a
steadystream ꢀduring the addition, the reaction temperature rose to À5ꢀC). The reaction mixture was
stirred at À10ꢀC for 3 h and then allowed to stand at room temperature overnight. The crystals that
precipitated were ®ltered off and washed 4 times with 100 cm3 of dist. H2O and 2 times with 100 cm3
toluene. The obtained 21.4 g of white crystalline powder ꢀ68%) were used for the next step. A small
sample was further puri®ed byrecrystallization.
Colourless crystals; m.p.: 166±168ꢀC ꢀMeOH); 1H NMR ꢀCDCl3): ꢁ ˆ 1.45±2.15 ꢀm, 3  CH2),
2.89 ꢀm, H-1), 4.19 ꢀm, H-2), 5.07 ꢀAB, J ˆ 12 Hz, OCH2Ph), 5.32 ꢀbs, CONH2), 5.45 ꢀbs,
CHNHCO), 5.60 ꢀbs, CONH2), 7.27±7.43 ꢀm, 5  CH) ppm; 13C NMR ꢀCDCl3): ꢁ ˆ 23.3 ꢀC4),
28.71 ꢀC5), 33.10 ꢀC3), 47.68 ꢀC1), 55.22 ꢀC2), 67.32 ꢀOCH2Ph), 128.75, 129.15 ꢀPh, C20±C60),
137.23 ꢀPh, C10), 157.08 ꢀNHCOO), 176.73 ꢀCONH2) ppm.
cis-2-Aminocyclopentanecarboxamide ꢀ2a; C6H12N2O)
cis-2-Benzyloxycarbonylaminocyclopentanecarboxamide ꢀ9; 20 g, 0.076 mol) were dissolved in
600 cm3 MeOH and hydrogenated in the presence of 2 g 10% Pd=C at atmospheric pressure at 40ꢀC
until the indicated amount of hydrogen was absorbed ꢀ8 h). The catalyst was removed by ®ltration.
After evaporation, 2a was obtained as a white crystalline powder ꢀ7.6 g, 78%) which was puri®ed by
recrystallization.
Colourless crystals; m.p.: 135±137ꢀC ꢀEtOAc); 1H NMR ꢀCDCl3): ꢁ ˆ 1.51±2.08 ꢀ6H, 3  CH2),
1.56 ꢀ2H, bs, CHNH2), 2.62 ꢀ1H, m, H-1), 3.56 ꢀ1H, m, H-2), 5.73 ꢀ1H, bs, CONH2), 6.74 ꢀ1H, bs,
CONH2) ppm, 13C NMR ꢀCDCl3): ꢁ ˆ 22.4 ꢀC4), 26.1 ꢀC5), 34.1 ꢀC3), 50.3 ꢀC1), 54.6 ꢀC2), 179.8
ꢀCONH2) ppm.
trans-2-Aminocyclopentanecarboxamide hydrochloride ꢀ3b; C6H13ClN2O)
cis-2-Aminocyclopentanecarboxamide ꢀ2a; 1.1 g, 8.6 mmol) was thoroughlymixed with sodium
methoxide ꢀ0.23 g, 4.3 mmol), and the mixture was maintained at 150ꢀC for 10 min. After cooling to
room temperature, the reaction mixture was washed with 3 Â 25 cm3 hot ethyl acetate and ®ltered.
After evaporation of the solvent, the 1H NMR spectrum of the crude product revealed 3a and 2a in a
ratio of 9:1. The hydrochloride of this mixture was prepared. Upon trituration of the residue with
ethyl acetate and EtOH, 0.45 g of a white crystalline powder were obtained. The hydrochloride 3b
was obtained by recrystallization ꢀyield 32%).
1
Colourless crystals; m.p.: 198±201ꢀC ꢀ90% EtOH); H NMR ꢀD2O): ꢁ ˆ 1.62±2.38 ꢀ3  CH2),
2.88 ꢀm, H-1), 3.86 ꢀm, H-2) ppm; 13C NMR ꢀD2O): ꢁ ˆ 23.5 ꢀC4), 30.6 ꢀC5), 30.9 ꢀC3), 49.4 ꢀC1),
54.3 ꢀC2), 178.5 ꢀCONH2) ppm.
cis-2-Aminocyclopentanecarboxamide hydrobromide ꢀ2c; C6H13BrN2O)
cis-2-Benzyloxycarbonylaminocyclopentanecarboxamide ꢀ9; 2.62 g, 10 mmol) was added to 8.8 cm3
33% HBr in glacial acetic acid. The solution was stirred for 1 h, during which time a precipitate was

ꢀ
P. Csomos et al.
1082
formed. To the suspension, 20 cm3 diethyl ether were added, and 1.80 g of white crystalline powder
were ®ltered off ꢀ86%), washed with diethyl ether, and puri®ed by recrystallization.
1
Colourless crystals; m.p.: 338±233ꢀC ꢀEtOH=Et2O); H NMR ꢀD2O): ꢁ ˆ 1.70±2.22 ꢀ3  CH2),
3.04 ꢀm, H-1), 3.87 ꢀm, H-2) ppm; 13C NMR ꢀD2O): ꢁ ˆ 21.9 ꢀC4), 28.5 ꢀC5), 30.6 ꢀC3), 45.7 ꢀC1),
53.8 ꢀC2), 177.9 ꢀCONH2) ppm.
6-tert-Butoxycarbonyl-6-azabicyclo[3.2.0]heptan-7-one ꢀ10; C11H17NO3)
6-Azabicyclo[3.2.0]heptan-7-one ꢀ4; 3.3 g, 30 mmol) was dissolved in 20 cm3 dryCH 2Cl2. The
solution was stirred, and 0.37 g 4-dimethylaminopyridine was added, followed by 7.2 g Boc2O
ꢀ33 mmol). After stirring at room temperature for 5 h, the reaction mixture was left overnight. The
brownish reaction mixture was then extracted with brine and dried ꢀNa2SO4). Evaporation left a pale-
yellow oil which was passed over a short column, with toluene:ethyl acetate ˆ 4:1 as eluent. After
evaporation, 5.26 g of 10 were obtained as a white crystalline powder upon trituration with n-hexane
ꢀ83%).
1
Colourless crystals; m.p.: 47±50ꢀC ꢀi-Pr2O); H NMR ꢀCDCl3): ꢁ ˆ 1.36±2.25 ꢀ3  CH2), 1.52
ꢀs, 3  CH3), 3.47 ꢀm, H-1), 4.33 ꢀm, H-2) ppm; 13C NMR ꢀ100 MHz, CDCl3): ꢁ ˆ 23.1 ꢀC3), 25.9
ꢀC2), 28.6 ꢀ3 Â CH3), 29.4 ꢀC4), 54.7 ꢀC1), 58.0 ꢀC5), 83.31 ꢀOCꢀCH3)3), 148.0 ꢀNCOO), 168.2
ꢀCON) ppm.
cis-2-tert-Butoxycarbonylaminocyclopentanecarboxamide ꢀ11; C11H20N2O3)
6-tert-Butoxycarbonyl-6-azabicyclo[3.2.0]heptan-7-one ꢀ10; 3 g, 14.2 mmol) was dissolved in
3
ꢀ
30 cm 25% solution of NH3 in dryMeOH. The reaction mixture was allowed to stand at 4 C for
12 h and was then evaporated, ®rst at room temperature and then on a 60ꢀC water bath. The white
crystalline powder obtained was puri®ed by recrystallization ꢀ2.50 g, yield 77%).
1
Colourless crystals; m.p.: 163±166ꢀC ꢀEtOAc); H NMR ꢀCDCl3): ꢁ ˆ 1.32±2.15 ꢀ3  CH2),
1.42 ꢀs, 3  CH3), 2.92 ꢀm, H-1), 4.14 ꢀm, H-2) ppm; 13C NMR ꢀCDCl3): ꢁ ˆ 23.3 ꢀC4), 28.5
ꢀC5), 29.0 ꢀ3 Â CH3), 33.2 ꢀC4), 47.9 ꢀC1), 54.8 ꢀC2), 80.1 ꢀOCꢀCH3)3), 156.7 ꢀNHCOO), 176.9
ꢀCONH2) ppm.
cis-2-Aminocyclopentanecarboxamide hydrochloride ꢀ2b; C6H13ClN2O)
cis-2-tert-Butoxycarbonylaminocyclopentanecarboxamide ꢀ11; 1.8 g, 7.9 mmol) was dissolved in
20 cm3 3 M HCl solution in EtOH. The reaction mixture was left to stand at room temperature for 2 h
and then evaporated at room temperature. After evaporation, 1.10 g 2b were obtained as a white
crystalline powder ꢀ85%) which was puri®ed by recrystallization.
1
Colourless crystals; m.p.: 243ꢀC ꢀEtOH=Et2O); H NMR ꢀD2O): ꢁ ˆ 1.70±2.22 ꢀ3  CH2), 3.04
ꢀm, H-1), 3.87 ꢀm, H-2) ppm; 13C NMR ꢀD2O): ꢁ ˆ 21.9 ꢀC4), 28.4 ꢀC5), 30.6 ꢀC3), 45.7 ꢀC1), 53.8
ꢀC2), 177.9 ꢀCONH2) ppm.
cis-N-Benzyl-2-tert-butoxycarbonylaminocyclopentanecarboxamide ꢀ12; C18H26N2O3)
6-tert-Butoxycarbonyl-6-azabicyclo[3.2.0]heptan-7-one ꢀ10; 1.59 g, 7.5 mmol) was dissolved in
50 cm3 dry toluene, and 0.81 g benzylamine ꢀ7.5 mmol) and a catalytic amount of p-toluenesulfonic
acid were added. The mixture was re¯uxed for 24 h, extracted with 5% NaHCO3 solution, dried
ꢀNa2SO4), and evaporated. The 2.20 g resulting white crystalline powder ꢀ92%) were puri®ed by
recrystallization.

2-Aminocyclopentanecarboxamides
1083
Colourless crystals; m.p.: 146±148ꢀC ꢀEtOAc); 1H NMR ꢀCDCl3): ꢁ ˆ 1.40 ꢀs, 3  CH3),
1.48±2.14 ꢀ3  CH2), 2.82 ꢀm, H-1), 4.11 ꢀqui, J ˆ 7.8, H-2), 4.41 ꢀAB system, J ˆ 8 Hz, coup. with
NH, NHCH2Ph), 5.10 ꢀb, CONHCH2), 6.05 ꢀbs, NHCOO), 7.20±7.38 ꢀm, 5 Â CH) ppm; 13C NMR
ꢀCDCl3): ꢁ ˆ 23.3 ꢀC4), 28.8 ꢀC5), 29.1 ꢀ3  CH3), 33.3 ꢀC3), 44.3 ꢀNCH2Ph), 48.7 ꢀC1), 54.9 ꢀC2),
79.9 ꢀOCꢀCH3)3), 128.1 ꢀPh, C40), 128.4 ꢀPh, C30, C50), 129.4 ꢀPh, C20, C60) 138.9 ꢀPh, C10), 156.6
ꢀNHCOO), 174.3 ꢀCHCON) ppm.
cis-N-Benzyl-2-aminocyclopentanecarboxamide ꢀ13; C13H19ClN2O)
cis-N-Benzyl-2-tert-butoxycarbonylaminocyclopentanecarboxamide ꢀ12; 0.7 g, 2.2 mmol) was
dissolved in a 3 M HCl solution in 20 cm3 dryEtOH. The reaction mixture was left to stand at
room temperature for 2 h and evaporated at room temperature. The 0.44 g obtained white crystalline
powder ꢀ78%) were puri®ed byrecrystallization.
Colourless crystals; m.p.: 150±153ꢀC ꢀi-Pr2O); 1H NMR ꢀCDCl3): ꢁ ˆ 1.70±2.28 ꢀ3  CH2), 3.04
ꢀm, H-1), 3.87 ꢀm, H-2), 4.41 ꢀAB, J ˆ 15.3, NHCH2Ph), 5.10 ꢀb, CONHCH2), 7.34±7.45 ꢀm,
5  CH) ppm; 13C NMR ꢀCDCl3): ꢁ ˆ 21.9 ꢀC4), 28.7 ꢀC5), 30.6 ꢀC3), 43.3 ꢀNCH2Ph), 46.1 ꢀC1),
53.9 ꢀC2), 127.6 ꢀPh, C30, C50), 127.9 ꢀPh, C40), 129.3 ꢀPh, C20, C60), 138.3 ꢀPh, C10), 175.0
ꢀCONH2) ppm.
Acknowledgements
We express thanks to the Hungarian Scienti®c Research Foundation for grants OTKA F032355 and
T030452.
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Received November 11, 2001. Accepted .revised) November 26, 2001